We have observed that several 6-(m-substituted phenyl) analogs of ethidium bromide are more effective than is ethidium bromide in stabilizing the DNA helix (as indicated by higher delta Tm values) and in inhibiting RNA synthesis in L1210 cells. Molecular models suggest that substituents in this meta position are well positioned in the intercalation complex with DNA to interact with specific sites in DNA by hydrogen bonding. Models also suggest that the meta position of the 6-phenyl group is an advantageous site for linking two phenanthridinium residues to create a potential double intercalator. We have prepared one such molecule and have found that it binds extremely tightly to DNA and presumably does double intercalate. We propose to synthesize several specific compounds, members of these two classes of phenanthridinium salts, and to study their interactions with DNA and with polynucleotides, using biophysical and biochemical measurements and assays.